1. Technical Field
This invention provides a medical device for simultaneously or sequentially delivering volumetric quantities of biochemically reactive fluids contained in separate containers and more particularly to a medical fluid delivery system for volumetrically delivering fibrinogen and thrombin to form fibrin on a surface.
2. Background Art
One of the major problems in intra-abdominal surgery is the avoidance of post-operative adhesions. It is well-known that adhesions contribute to pain, immobility, retarded wound healing, and in particular to intestinal obstruction which even may be life-threatening. In the field of gynecological surgery, post-surgical adhesions involving female reproductive organs may result in infertility.
Each surgical procedure necessarily produces various forms of trauma where the abdominal cavity or other human cavity is opened for an inspection. Physiologically, the process of wound closure then starts when bleeding ceases upon formation of a hemostatic clot at the places where blood vessels are injured. The clot, at first comprising mainly platelets, is solidified by a fibrin network resulting from the activation of an enzyme cascade involving thrombin, factor XIII and calcium. Further steps on the way to the sealing of the wound are retraction of the hemostatic clot, invasion of various cell types including fibroblasts into the wound area and eventually the lysis of the fibrin network. Adhesions are thought to begin to form when the fibrin clot covering an injury comes into contact with an adjacent surface and the new connective tissue produced by the fibroblasts attach the two surfaces together.
The problems associated with adhesions often require a further operative procedure for removing/lysing the adhesions, called adhesiolysis, which, like the first operation, principally bears the risk of forming additional adhesions.
Accordingly, the prevention of adhesion formation is medically important. Among the different approaches for prevention of adhesion formation, one involves the use of materials as a physical or bio-mechanical barrier for the separation or isolation of traumatized tissues during the healing process. Both synthetic materials and natural materials have been used as a barrier to adhesion formation. Permanent, inert implants like Gore Tex(copyright) surgical membranes consisting of expanded polytetrafluoroethylene (PTFE) generally require a second operative procedure to remove them, while others such as surgical membranes of oxidized regenerated cellulose are biodegradable, but are thought to elicit an inflammatory response ultimately leading to adhesion formation (A. F. Haney and E. Doty, Fertility and Sterility, 60, 550-558, 1993).
Fibrin sealants/glues are well-known in the art for use in hemostasis, tissue sealing and wound healing, and have been commercially available outside the United States for more than a decade. Fibrin glues have not been widely used for anti-adhesion purposes. Further, the practice of changing the concentrations of thrombin and fibrinogen to achieve a fibrin film having a desired pore size is also not widely practiced.
Fibrin glues mimic the last step of the coagulation cascade and are usually commercialized as kits comprising two main components. The first component is a solution comprising fibrinogen and optionally factor XIII, while the second component is a thrombin calcium solution. After mixing these components, the fibrinogen is proteolytically cleaved by thrombin and thus converted into fibrin monomers. Factor XIII is also cleaved by thrombin into its activated form (FXIIIa). FXIIIa cross links the fibrin monomers to form a three-dimensional network commonly called xe2x80x9cFibrin Gel.xe2x80x9d
Previous attempts to provide a thrombin and fibrinogen delivery device are known.
For example, one such device is disclosed in U.S. Pat. No. 4,978,336 which discloses a dual syringe system. A device made by the assignee of the ""336 Patent, Hemaedics, Inc., is sold under the tradename DUOFLO(trademark). Each syringe distal end is attached to a common manifold 14 having a mixing chamber. Fibrinogen and thrombin solutions are mixed in the manifold 14 prior to application to a wound or other surface. The manifold has a discharge tip for delivering the mixed solution onto a surface. The shortcoming of this device is the propensity for the tip to clog. This occurs when solid fibrin is formed upon brief interruptions in the application process. Such interruptions are common in normal medical procedures. The likelihood of this occurring increases as the thrombin concentration increases especially thrombin concentrations of greater than 20 IU/ml. The ""336 Patent acknowledges the clogging problem and suggests solving the problem by replacing the clogged tip. (Col. 3, line 4-Col. 4, line 2). However, replacing clogged tips is impractical and unacceptable for minimally invasive surgeries where a cavity of an animal body is accessed through a small surgical opening.
Other techniques provide for applying beads of a solution of thrombin and calcium and a solution of fibrinogen and Factor XIII adjacent and in contact with one another on a surface. In this case, the thrombin and fibrinogen react primarily along interfacing surfaces while the remaining portions of the solutions are generally isolated from one another by the solid fibrin formed between them. Thus, there is inadequate mixing of the solutions to provide for a suitable fibrin film. Also, the unreacted fibrinogen is available to react with thrombin supplied by the body to promote the formation of adhesions.
U.S. Pat. No. 4,631,055 discloses another thrombin and fibrinogen delivery device having two syringes mounted in a holding frame 3 in parallel spaced relationship. A conical portion of a distal end each syringe is inserted into a connecting head. In one embodiment of the ""055 patent, mixing of fluids contained in each syringe occurs inside the connecting head and in another embodiment the mixing of the fluids occurs outside the mixing head. The connecting head also includes a channel to supply medicinal gas under pressure. The medicinal gas contacts the fluids at a mouth of the connecting head and conveys the fluids contained in the syringes to a surface.
Product literature commenting on a dual syringe device for delivering fibrinogen and thrombin and sold by the Assignee of the ""055 patent, reports that the device operates at gas pressures of about 30-65 psi. The momentum of the pressurized gas, especially when conveying entrained fluids, could possibly cause damage to tissue being treated by this device.
Similarly, U.S. Pat. No. 5,582,596 to Fukunaga et al. discloses an applicator useful for applying a biocompatible adhesive containing human or animal protein to a surgical site of a living body. The applicator consists of a pair of syringes, each including a barrel and a nozzle at one end of the barrel, and a spray head. The nozzles of the syringes are adapted to be fitted with the spray head. The spray head comprises a housing, a pair of sterile gas ejecting nozzles in the housing, a sterile gas supply tube, and a pair of solution tubes arranged such that when the solutions are fed from the syringes they are conveyed through the solution tubes and ejected therefrom. The spray head is adapted to spray the protein and coagulation solutions fed from the syringes by ejection of a sterile gas. Thus, like the ""055 Patent the pressurized gas that entrains the fluids contact the tissue surfaces.
Further, a device sold by Johnson and Johnson provided for applying a bovine thrombin and calcium chloride solution to a wound. In addition to possible issues raised by the use of bovine proteins, this procedure does not provide satisfactory hemostasis function in high blood flow situations. The thrombin is believed to be washed from the wound site by the flow of blood.
One prior attempt at creating a medical fluid delivery system which eliminates the likelihood of clogging in the exit ports of the system is disclosed in U.S. Pat. No. 5,368,563, issued on Nov. 29, 1994 to Lonneman et al. This large-dimensioned sprayer assembly for a fibrin glue delivery system includes at least one solution reservoir attached to an ejection port for spraying the solution onto a treatment site. Atomization is achieved mechanically using a multi-piece assembly including a base plate and sprayer plate. Ejection ports of the device emit separately atomized droplets of solutions which mix with one another while airborne and upon contact with the wound, thus eliminating clogging of the ejection ports by mixtures of the solutions prior to ejection from the device. The ejection ports are separated by a distance such that spray from one port does not contaminate the other port.
While such a device is suitable for invasive surgeries involving substantial incisions in which the operator of the device has a great deal of clearance for insertion of the device, such an assembly is unsuitable for use during minimally invasive surgeries in which the delivery system must be manipulated within standard trocar-sized openings. Furthermore, the multi-piece assembly of the sprayer unit creates cumbersome assembly steps.
An additional problem encountered with hand held devices for delivering thrombin and fibrinogen results from the high viscosity of fibrinogen. Fresh fibrinogen, has a viscosity of 56 cp and frozen/thawed fibrinogen (Hyland standard concentration) has a viscosity of 90-200 cp or more. It has been found by the present inventors that a hand-pressurized device, without pressure assistance from outside sources, was only capable of generating sufficient pressure to spray solution of 15 cp or less with a 10 cc or 20 cc syringe. Thus, these hand-pressurized devices could not be used to deliver fibrinogen in full concentration as received in kits using a 10 cc or 20 cc syringe.
U.S. Pat. No. 5,376,079 to Holm et al. provides a mechanical device for delivering fibrinogen and thrombin contained in separate syringe barrels. The device of the ""079 provides ratchet mechanisms for simultaneously applying thrombin and fibrinogen upon pulling a trigger. The ""079 Patent provides a second embodiment that provides a lever 68 for administering a small amount of the fluid contained in the first syringes without applying the component contained in the second syringe. However, this embodiment does not allow for applying the fluid contained in the second syringe without also applying the fluid in the first syringe. The ""079 Patent also does not provide for atomizing the thrombin and fibrinogen onto a surface.
U.S. Pat. No. 5,656,035 to Avoy et al. discloses a fibrinogen and thrombin dispensing device for separately spraying fibrinogen and thrombin solutions, The ""035 Patent discloses a radially-shaped spray head for spraying fibrinogen and thrombin inside of a stent (see FIG. 6) or on the outside of a tube (FIG. 9) and for inserting inside of a endoscope, arthroscope or gastroscope. The radially-shaped spray head has circumferentially spaced spray outlets about the spray head. The ""035 Patent discloses applying the fibrinogen and thrombin for hemostasis and tissue adhesive purposes. No mention is made of using the device of the ""035 Patent for antiadhesion purposes. There is also no mention in the ""035 Patent of adapting the radial spray head to minimize the incidence of adhesion formation incident to using the radial spray head. Because the radial spray head of the ""035 Patent requires spraying fibrinogen and thrombin in opposite directions in treating a wound, fibrinogen and thrombin will necessarily be sprayed on tissue across from a wound site and adjacent the wound site in treating the wound. It is likely that such indiscriminate spraying of fibrinogen and thrombin for hemostasis purposes shall lead to adhesion formation.
This invention overcomes these and other shortcomings in the prior art devices.
The present invention provides a medical device for delivering volumetric quantities of a first and a second biochemically reactive fluid. The device has a first container to contain the first biochemically reactive fluid and a second container to contain the second biochemically reactive fluid. An atomizer is in fluid communication with the first and second containers for separately atomizing the first and second biochemically reactive fluids into an aerosol with at least one energy source of a liquid energy, a mechanical energy, a vibration energy, and an electric energy. A fluid pressurizer is provided for delivering a third fluid under pressure to the first container to deliver the first fluid under pressure to the atomizer. A mechanical pressurizer is positioned within the second container for delivering the second fluid under pressure to the atomizer. This device could be modified so that the fluid pressurizer pressurizes the first and second fluids.
The present invention also provides a method for delivering biochemically reactive components to a surface comprising the steps of: (1) providing a first liquid solution of a first biochemically reactive component; (2) providing a second liquid solution of a second biochemically reactive component; (3) providing an atomizer in fluid communication with the first reactive component and the second reactive component, the atomizer being capable of separately atomizing the first reactive component and the second reactive component into an aerosol with at least one energy source of a liquid energy, a mechanical energy, a vibration energy, and an electric energy; (4) delivering a fluid under pressure to force the first reactive component under pressure to the atomizer to spray the first reactive component without the fluid; and (5) delivering the second reactive component under pressure to the atomizer to spray the second reactive component.
The present invention further provides a medical device for delivering volumetric quantities of a first and a second biochemically reactive fluid having a body having a grip section and a barrel section. a first container for containing the first fluid and a second container for containing the second fluid, the first container and the second container being carried by the body; a first pressurized fluid cylinder carried by the body and in fluid communication with the first container; and an atomizer connected to the body and in fluid communication with the first container and the second container for separately atomizing the first and second biochemically reactive fluids into an aerosol with at least one energy source of a liquid energy, a mechanical energy, a vibration energy, and an electric energy.
The present invention further provides a medical device for delivering volumetric quantities of a first and a second biochemically reactive fluid and a catalyst. The device has a first container to contain the first biochemically reactive fluid and a second container to contain the second biochemically reactive fluid. An atomizer is provided in fluid communication with the first channel and the second containers for separately atomizing the first and second biochemically reactive fluids into an aerosol with at least one energy source of a liquid energy, a mechanical energy, a vibration energy, and an electric energy. The device further includes a third channel for delivering a catalyst to influence a reaction between the first and second fluids. The device can also include more than 3 channels and can be used for numerous purposes as will be set forth below.